Scientists at The Scripps Research Institute (TSRI) have solved the mystery of why a specific signaling pathway can be associated with alcohol dependence. This signaling pathway is regulated by a gene called neurofibromatosis type 1 (Nf1), which TSRI scientists found is linked with excessive drinking in mice. The new research shows Nf1 regulates gamma-aminobutyric acid (GABA), a neurotransmitter that lowers anxiety and increases feelings of relaxation. “This novel and seminal study provides insights into the cellular mechanisms of alcohol dependence,” said TSRI Associate Professor Marisa Roberto, a co-author of the paper. “Importantly, the study also offers a correlation between rodent and human data.” In addition to showing that Nf1 is key to the regulation of the GABA, the research, which was published online on August 18, 2014 in Biological Psychiatry, shows that variations in the human version of the Nf1 gene are linked to alcohol-dependence risk and severity in patients. Dr. Pietro Paolo Sanna, associate professor at TSRI and the study’s corresponding author, was optimistic about the long-term clinical implications of the work. “A better understanding of the molecular processes involved in the transition to alcohol dependence will foster novel strategies for prevention and therapy,” he said. Researchers have long sought a gene or genes that might be responsible for risk and severity of alcohol dependence. “Despite a significant genetic contribution to alcohol dependence, few risk genes have been identified to date, and their mechanisms of action are generally poorly understood,” said TSRI Staff Scientist Dr. Vez Repunte-Canonigo, co-first author of the paper with TSRI Research Associate Dr. Melissa Herman.